Their findings were described in a letter published in the January issue of JAMA Neurology.

The researchers used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, which was launched in 2003 as a public–private partnership.

The primary goal of ADNI is to test whether serial MRI, positron emission tomography, other biological markers, and clinical and neuropsychological assessments can be combined to measure the progression of mild cognitive impairment and early AD.

The current study looked at the level of ferritin in cerebrospinal fluid (CSF), which indicates the brain iron load. According to Dr Bush, it has been known since the 1950s that elevated iron is a pathologic feature of AD. Iron elevation, he said, may cause oxidative stress,which damages neurons.

People who express the APOE ε4 allele are at a high risk for cognitivedecline, although not all will do so.

"The study found that in cognitively normal people who express the APOE ε4 risk allele, high CSF ferritin almost perfectlypredicted whether the individual will experience cognitive decline in the subsequent 7 years," said Dr Bush.

The effect of ferritin "was far greater than the mostestablished biomarkers — tau and amyloid β," he said.

Their results also showed that APOE ε4 carriers who have low iron levels were protected from cognitive decline.

The study is important because it shows that the CSF ferritin level is "an excellent biomarker for predicting whether someone with APOE ε4 might progressin the foreseeable future," said Dr Bush.

CSF ferritin or other iron biomarkers — for example, MRI techniques, such as quantitative susceptibility mapping — could be used in the clinic to predict the likely progression of cognitive decline in patients, said Dr Bush.

These biomarkers could also be used forclinical trial recruitment, he said.

Dr Bush and colleagues will be launching a phase 2b clinical trial to determine whether deferiprone, a brain-permeable drug that chelates iron, can slow disease progression among patients in the early stagesof Alzheimer's disease.

Dr Bush is a shareholder in Prana Biotechnology Pty Ltd, Cogstate Pty Ltd, Eucalyptus Pty Ltd, Mesoblast Pty Ltd, Brighton Biotech LLC, Nextvet Ltd, Grunbiotics Pty Ltd, and Collaborative Medicinal Development LLC and a paid consultant for Collaborative Medicinal Development Pty Ltd. He and the other authors have filed a provisional patent encompassing findings from these data. Dr Bush has received funding relevant to this study from the Australian National Health and Medical Research Council, the Alzheimer's Association, Alzheimer's Research UK, the Michael J. Fox Foundation for Parkinson's Research, the Weston Brain Institute, and the Perpetual-Salteri Foundation.